1. Field of the Invention
The present invention relates to an apparatus and method for separating components of a fluid. The invention has particular advantages in connection with separating blood components.
This application is related to U.S. Pat. No. 5,674,173, issued on Oct. 7, 1997, U.S. patent application Ser. No. 08/676,039, filed on Jul. 5, 1996 (pending), and U.S. patent application Ser. No. 08/853,374, filed on May 8,1997 (pending). The entire disclosures of U.S. Pat. No. 5,674,173 and U.S. patent applications Ser. Nos. 08/676,039 and 08/853,374 are incorporated herein by reference.
2. Description of the Related Art
In many different fields, liquids carrying particle substances must be filtered or processed to obtain either a purified liquid or purified particle end product. In its broadest sense, a filter is any device capable of removing or separating particles from a substance. Thus, the term xe2x80x9cfilterxe2x80x9d as used herein is not limited to a porous media material but includes many different types of processes where particles are either separated from one another or from liquid.
In the medical field, it is often necessary to filter blood. Whole blood consists of various liquid components and particle components. Sometimes, the particle components are referred to as xe2x80x9cformed elementsxe2x80x9d. The liquid portion of blood is largely made up of plasma, and the particle components include red blood cells (erythrocytes), white blood cells (including leukocytes), and platelets (thrombocytes). While these constituents have similar densities, their average density relationship, in order of decreasing density, is as follows: red blood cells, white blood cells, platelets, and plasma. In addition, the particle constituents are related according to size, in order of decreasing size, as follows: white blood cells, red blood cells, and platelets. Most current purification devices rely on density and size differences or surface chemistry characteristics to separate and/or filter the blood components.
Numerous therapeutic treatments require groups of particles to be removed from whole blood before either liquid or particle components can be infused into a patient. For example, cancer patients often require platelet transfusions after undergoing ablative, chemical, or radiation therapy. In this procedure, donated whole blood is processed to remove platelets and these platelets are then infused into the patient. However, if a patient receives an excessive number of foreign white blood cells as contamination in a platelet transfusion, the patient""s body may reject the platelet transfusion, leading to a host of serious health risks.
Typically, donated platelets are separated or harvested from other blood components using a centrifuge. The centrifuge rotates a blood reservoir to separate components within the reservoir using centrifugal force. In use, blood enters the reservoir while it is rotating at a very rapid speed and centrifugal force stratifies the blood components, so that particular components may be separately removed. Centrifuges are effective at separating platelets from whole blood, however they typically are unable to separate all of the white blood cells from the platelets. Historically, blood separation and centrifugation devices are typically unable to consistently (99% of the time) produce platelet product that meets the xe2x80x9cleukopoorxe2x80x9d standard of less than 5xc3x97106 white blood cells for at least 3xc3x971011 platelets collected.
Because typical centrifuge platelet collection processes are unable to consistently and satisfactorily separate white blood cells from platelets, other processes have been added to improve results. In one procedure, after centrifuging, platelets are passed through a porous woven or non-woven media filter, which may have a modified surface, to remove white blood cells. However, use of the porous filter introduces its own set of problems. Conventional porous filters may be inefficient because they may permanently remove or trap approximately 5-20% of the platelets. These conventional filters may also reducexe2x80x9cplatelet viability,xe2x80x9d meaning that once passed through a filter a percentage of the platelets cease to function properly and may be partially or fully activated. In addition, porous filters may cause the release of brandykinin, which may lead to hypotensive episodes in a patient. Porous filters are also expensive and often require additional time consuming manual labor to perform a filtration process.
Although porous filters are effective in removing a substantial number of white blood cells, they have drawbacks. For example, after centrifuging and before porous filtering, a period of time must pass to give activated platelets time to transform to a deactivated state. Otherwise, the activated platelets are likely to clog the filter. Therefore, the use of at least some porous filters is not feasible in on-line processes.
Another separation process is one known as centrifugal elutriation. This process separates cells suspended in a liquid medium without the use of a membrane filter. In one common form of elutriation, a cell batch is introduced into a flow of liquid elutriation buffer. This liquid which carries the cell batch in suspension, is then introduced into a funnel-shaped chamber located in a spinning centrifuge. As additional liquid buffer the chamber, the liquid sweeps smaller sized, slower-sedimenting cells toward an elutriation boundary within the chamber, while larger, faster-sedimenting cells migrate to an area of the chamber having the greatest centrifugal force.
When the centrifugal force and force generated by the fluid flow are balanced, the fluid flow is increased to force slower-sedimenting cells from an exit port in the chamber, while faster-sedimenting cells are retained in the chamber. If fluid flow through the camber is increased, progressively larger, faster-sedimenting cells may be removed from the chamber.
Thus, centrifugal elutriation separates particles having different sedimentation velocities. Stoke""s law describes sedimentation velocity (SV) of a spherical particle as follows:   SV  =            2      9        ⁢                            r          2                ⁢                  (                                    ρ              p                        -                          ρ              m                                )                ⁢        g            η      
where, r is the radius of the particle, xcfx81p is the density of the particle, xcfx81m is the density of the liquid medium, xcex7 is the viscosity of the medium, and g is the gravitational or centrifugal acceleration. Because the radius of a particle is raised to the second power in the Stoke""s equation and the density of the particle is not, the size of a cell, rather than its density, greatly influences its sedimentation rate. This explains why larger particles generally remain in a chamber during centrifugal elutriation, while smaller particles are released, if the particles have similar densities.
As described in U.S. Pat. No. 3,825,175 to Sartory, centrifugal elutriation has a number of limitations. In most of these processes, particles must be introduced within a flow of fluid medium in separate discontinuous batches to allow for sufficient particle separation. Thus, some elutriation processes only permit separation in particle batches and require an additional fluid medium to transport particles. In addition, flow forces must be precisely balanced against centrifugal force to allow for proper particle segregation.
Further, a Coriolis jetting effect takes place when particles flow into an elutriation chamber from a high centrifugal field toward a lower centrifugal field. The fluid and particles turbulently collide with an inner wall of the chamber facing the rotational direction of the centrifuge. This phenomenon mixes particles within the chamber and reduces the effectiveness of the separation process. Further, Coriolis jetting shunts flow along the inner wall from the inlet directly to the outlet. Thus, particles pass around the elutriative field to contaminate the end product.
Particle mixing by particle density inversion is an additional problem encountered in some prior elutriation processes. Fluid flowing within the elutriation chamber has a decreasing velocity as it flows in the centripetal direction from an entrance port toward an increased cross sectional portion of the chamber. Because particles tend to concentrate within a flowing liquid in areas of lower flow velocity, rather than in areas of high flow velocity, the particles concentrate near the increased cross-sectional area of the chamber. Correspondingly, since flow velocity is greatest adjacent the entrance port, the particle concentration is reduced in this area. Density inversion of particles takes place when the centrifugal force urges the particles from the high particle concentration at the portion of increased cross-section toward the entrance port. This particle turnover reduces the effectiveness of particle separation by elutriation.
For these and other reasons, there is a need to improve particle separation.
The present invention is directed to an apparatus and method that substantially obviate one or more of the limitations and disadvantages of the related art. To achieve these and other advantages and in accordance with the purpose of the invention, as embodied and broadly described herein, the invention includes an apparatus for use with a centrifuge having a rotatable rotor including a retainer. The apparatus comprises a separation vessel for placement in the retainer. The separation vessel has an inlet portion, an outlet portion, and a flow path extending between the inlet portion and the outlet portion. The inlet portion has an inlet port for supplying to the separation vessel a fluid to be separated into components. The outlet portion includes a first wall, a second wall spaced from the first wall, at least three outlet ports for removing separated components of the fluid from the separation vessel, and a shield between one of the outlet ports and the second wall for limiting entry into said one outlet port of at least one relatively high density component of the fluid. The shield has a surface facing said one outlet port. When the separation vessel is placed in the retainer, the surface of the shield is located closer than two of the other outlet ports to the axis of rotation to maintain the surface of the shield out of a layer of the relatively high density fluid component formed in the outlet portion.
In one other aspect, the invention includes a centrifugal separation apparatus having a centrifuge rotor, a retainer on the centrifuge rotor, and a separation vessel in the retainer. The separation vessel includes an inlet portion, an outlet portion, and a trap dam. The outlet portion has a barrier for substantially blocking passage of at least one of the separated components of the fluid, and at least one outlet port for removing at least the blocked component of the fluid from the vessel. The trap dam is located between the outlet port and the inlet portion. The trap dam extends away from the axis of rotation of the rotor to trap relatively low density substances and includes a downstream portion having a relatively gradual slope.
In an additional aspect, the separation vessel further includes a gradual sloped segment across from the trap dam. The gradual sloped segment increases thickness of a layer of the relatively high density fluid component formed across from the trap dam.
In another aspect, the invention includes an apparatus having a separation vessel and a fluid chamber. The separation vessel includes an inlet port, a first outlet port for removing at least relatively intermediate density components of fluid, and a second outlet port for removing at least one relatively low density component of the fluid. A first line is coupled to the first outlet port and also is coupled to an inlet of a fluid chamber for separating the components of the fluid flowing through the first line. A second line is coupled to the second outlet port and is also in flow communication with an outlet of the fluid chamber to mix the relatively low density component of the fluid with substances flowing from the outlet of the fluid chamber.
In yet another aspect, the invention includes a method of separating components of a fluid. In the method, a separation vessel rotates about an axis of rotation and fluid to be separated passes into the vessel. The fluid separates into at least a relatively high density component, a relatively intermediate density component, and a relatively low density component. At least the relatively intermediate density component is removed from the separation vessel via an outlet port. Passage of the relatively high density component into the outlet port is limited with a shield having a surface facing the outlet port. The position of an interface between the high density component and the intermediate density component is controlled so that the surface of the shield is between the interface and the outlet port.
In still another aspect, the high density component includes red blood cells, the intermediate density component includes platelets, and the low density component includes plasma.
In an additional aspect, the invention includes a method wherein at least relatively intermediate density components are removed from the separation vessel via a first outlet port; and at least some of a low density component is removed from the separation vessel via a second outlet port. The removed intermediate density components are flowed into a fluid chamber. At least some of a first subcomponent of the intermediate density components is retained in the fluid chamber, and at least some of a second subcomponent of the intermediate density components is permitted to flow from an outlet of the fluid chamber. The low density component removed from the separation vessel is combined with the second subcomponent flowing from the outlet of the fluid chamber.
In a further aspect of the invention, the first subcomponent includes white blood cells, the second subcomponent includes platelets, and the low density component includes plasma.
In an even further aspect of the invention, an apparatus for use with a centrifuge includes a separation vessel having an outlet portion including at least one outlet port and a shield having a surface facing the outlet port. Structure is provided for controlling the position of an interface between at least one relatively high density component of a fluid and at least one other separated component of the fluid so that the surface of the shield is between the interface and the outlet port.
In another aspect, the invention includes a method of reducing clumping of platelets during separation of blood components. The method includes introducing blood components into a rotating separation vessel such that the blood components stratify in the separation vessel to form at least a radial outer layer including red blood cells, an intermediate layer including at least platelets, and a radial inner layer including low density substances. To substantially limit contact between the platelets and at least one of the radial inner and outer walls of the separation vessel, the radial outer layer of red blood cells is maintained between the intermediate layer and the radial outer wall of the separation vessel and/or the radial inner layer of low density substances is maintained between the intermediate layer and the radial inner wall of the separation vessel. This reduces platelet clumping.
It is to be understood that both the foregoing general description and the following detailed description are exemplary, and are intended to provide further explanation of the invention as claimed.